The aim of the investigation is to characterize the relationship between growth rate and the metabolism of histones and other chromosomal proteins. Growth will be measured primarily by the incorporation of H3-labeled thymidine into DNA of regenerating liver and Morris hepatomas in the rat showing a spectrum of growth rates. The influence of agents which inhibit DNA synthesis will be studied on the synthesis and phosphorylation of nuclear proteins. Attention will be directed to the effects of growth regulating compounds on changes in nuclear protein synthesis which have been established in rapidly growing tissues by isotope incorporation, polyacrylamide gel electrophoresis and isoelectric focusing. The compounds to be studied include hydroxyurea and analogues and thiaxanthenones related to Miracil D. The action of these agents will be compared with the effect of X-irradiation and an attempt will be made to establish the degree of reversibility of changes in rapidly growing tissues. By comparison of regenerating liver and hepatomas, it may be possible to identify changes which are more characteristic of malignant than normal growth.